Your Gut Might Influence Whether or Not You Get Alzheimer's Disease

Alzheimer’s disease is a chronic neurodegenerative disease that is associated with cognitive decline. Among 25 million patients worldwide who suffer from dementia, 50 to 70 percent are suffering from AD. The disorder affects 4.4 percent of people over the age of 65 and 9.7 percent of those over the age of 70; the numbers roughly double every 5 years over the age of 65 (1). Early onset AD (familial) before age 65 is very uncommon, occurring at a rate of just 1 to 5 percent. The majority of patients afflicted with AD develop the disease after age 65.

The exact causes and pathophysiological nature of the disease are currently under intense investigation. One of the most recognized pathological events in the cause and progress in AD is the aggregation of a protein amyloid-beta (Aβ) in the brain. This protein (Aβ) has many functions in the brain and also in the gut. Incorrect breakdown of the protein leads to inflammation, excitotoxicity, neurofibrillary tangles, amyloid plaques, and ultimately leading to cellular death and cognitive and behavioral abnormalities.

Recently, the connection between gut microbiota and AD has shed some light on this pathology. Specifically, increased levels of Bacteroidetes (beneficial bacteria for humans) and decreased Firmicutes and Actinobacteria (primarily Bifidobacterium) in the gut microbiome are associated with AD (2). In one study, the researchers quantified the microbiome associated with AD. They characterized the bacterial taxonomic composition of fecal samples from participants with and without AD. They found that AD participants have a less diverse gut microbiome compared to age and sex-matched controls (2).

Interestingly, changes in these same bacteria, Firmicutes and Bacteroidetes, have also been associated with disorders such as type 2 diabetes, obesity, and Parkinson’s disease. Both diabetes and obesity are risk factors for AD. This indirectly implies that antibiotics that manipulate the gut microbiome can alter the development of AD. Some animal studies have demonstrated just that! In one study that used a mouse model, antibiotics changed the diversity of the gut microbiome (3). The resulting changes in the gut decreased beta-amyloid accumulations and decreased neuroinflammation in the plaque afflicted brain regions.

The gut microbiota is also a significant source of amyloids. Although the gut amyloids differ from amyloids in the central nervous system, they do have similarities (remember, the accumulation of amyloids in the brain is a key mechanism in the development of AD). One intriguing possibility is that bacterial amyloid proteins in the gut may cause priming of the immune system. This enhanced immune system response to the gut may lead to increased amyloids in the brain (4). This increase in brain amyloid can set the stage for the development of AD.

The enteric nervous system is a separate nervous system found in the gut. It is dedicated to gastrointestinal functioning. The enteric system communicates with the brain via multiple mechanisms including neurotransmitters (serotonin is mostly made in the gut). The enteric nervous system provides an opportunity for the gut to modulate brain functions and diseases. For example, in 80 percent of patients with Parkinson’s disease (PD), gastrointestinal dysfunction precedes motor function (4). Thus, gut problems can provide earlier markers of brain pathologies. In animal studies, mice with mutations in gene-related to beta amyloids, exhibit accumulation of amyloids (just like humans with AD), inflammations and gastrointestinal problems (5).

The proposed connection between the gut and AD is concerning in light of the increase in gut-related problems such as leaky gut, gut inflammation, and altered microbiomes. On the positive side, this connection can also point to therapeutic targets for AD. Some promising treatments include reducing inflammation, increasing good gut bacteria (probiotic supplementation), decreasing harmful bacteria, protecting the gut barrier and avoiding any gut irritants. In a clinical study employing some of these targets, supplementation of Lactobacilli and Bifidobacteria- based probiotics significantly improved the Mini-Mental State Examination scores in AD patients (6). A more provocative potential treatment is fecal microbiota transplantation from healthy young donors to the elderly. Finally, a healthy anti-inflammatory probiotic-rich diet seems to be a preventative panacea for many disorders.